Uncharted Territory: How the processing of smell differs from other senses

Anyone who has used a map (or as it’s more commonly called today, a smart phone) knows that it’s not so hard to turn the three-dimensional world into a useful 2-D representation. In fact, our brains do it instinctively. Spatial information enters via the retina, is carried along through the optic nerve and a few synapses, and eventually creates a wave of activity in the occipital lobe of the brain. This allows the external world to be mapped out in two dimensions across the surface of the visual cortex (with cells next to each other encoding areas of the visual field that are next to each other). The auditory system has an analogous process, although it may seem less intuitive. The cochlear, the snail-shaped organ in your inner ear, is responsible for creating a map of the frequencies of sounds. As that information gets passed along, low frequency stimuli end up being processed in one end of the auditory cortex and high frequencies at the other. The somatosensory cortex is similarly mapped; cortical areas getting input from your hand are next to those getting input from your wrists, etc. But when it comes to smell, everything is a bit…muddled.

See, the organization of the cells that process smells isn’t quite so straightforward. There is not what we would call an “olfactory map” in the cortex, at least not one that scientists can recognize. The pipeline of getting information from the nose into the brain is actually a quite intriguing one. It starts with the olfactory receptor neurons in the nose coming in contact with whatever molecules are floating about in the air. Different olfactory receptor neurons will bind to different molecules, and when this happens these receptor cells become active. They then project to big chunks of cells in the olfactory bulb called glomeruli, and in turn activate these cells. Each glomerulus will only get inputs from olfactory receptor cells that respond to the same odor molecule. So there is a great convergence of information, with each glomerulus responding to specific odorants. But it all appears to be for naught, because at the very next stage of processing things get all tangled up again. The cells in the glomeruli project to the piriform cortex, but in a random way which destroys the order and segregation they initially had. Cells in the piriform cortex thus get input from a variety of receptor types and respond to specific odors based on that input. However, we don’t have the same kind of physical relationship amongst cells that we see in other sensory modalities. That is, one cell’s response to a stimulus may have nothing in common to the response of the cell directly next to it. Cell A can be highly active when there is a hint of vanilla in the air and its neighbor cell B may fire in response to a whiff of vinegar.

This is odd because we generally view maps in cortex as serving some kind of purpose. To start, It’s energetically advantageous to have most of your connections be to nearby cells. If these connections are excitatory then it would nice if those nearby cells are trying to send a similar message. With this setup, local connections can be used to strengthen the signal, and with the addition of inhibitory interneurons that project farther away, weaken an opposing signal that’s a little way down the cortex. Basically, it’s easier to enhance the response of similarly-responsive cells and suppress the activity of unrelated cells if there is some meaningful layout to the cell landscape. But from our current vantage point, olfactory cortex looks like a complete jumble with no structure to be found.

But then again, what kind of structure would we expect? With visual cortex it’s easy: areas that are physically close to each other in the external world should be represented by cells that are physically close to each other in the cortex. A similar notion is true for auditory cortex: frequencies that are near each other should activate cells that are near each other. But what makes a smell “near” another smell? The molecules that activate olfactory receptors, the physical things that make up what we know as smells, can have complex molecular structures that vary in numerous dimensions. One could compare, for example, molecular size, the number of carbon atoms, or what functional groups are attached to the end of a molecule. Haddad et al.  actually came up with 1,664 different metrics to describe an odorant. Given all these different scales, to say that one odor molecule is similar to another doesn’t have much practical meaning. Especially when we consider the fact that molecules which are incredibly similar physically can elicit completely different perceptual experiences. For example, carvone is a molecule that can smell like spearmint, but if it’s structure is switched to the mirror opposite form, it elicits the spicy scent of caraway seeds. So the notion of the brain being able to create a map of smells presupposes the existence of a simple relationship amongst odorants, which simply doesn’t exist.

As with most mysteries of science, though, it presents a great opportunity. That is, the opportunity to be wrong. Perhaps piriform cortex does in fact have a grand organizing principle that is simply alluding our detection. The Sobel lab has produced some interesting work connecting odorant structure, receptor activity, and the perceived pleasantness of an odor. If they are able to find some kind of odor pleasure map, it would represent a new kind of topography for sensory cortex: one that is based on internal perception, not just external physical properties. This would produce a flood of new questions about how such organization develops, and the universality of smell preferences across species and individuals. What currently looks to our electrodes as evolution’s mistake, could in fact be a very well planned-out olfactory citymap. And learning how to read that map could lead to a whole new way of understanding our olfactory world.